Presently used techniques for non-invasive examination of a body use X-ray (e.g., computerized tomography) and ultrasound procedures. Another non-invasive procedure uses nuclear magnetic resonance (NMR) to obtain a cross-sectional image of the nuclei densities within a body. The average atomic number (Z) of nuclei in tumors tends to be significantly different from that of normal tissue. Hydrogen nuclear densities detected by NMR techniques are presently considered a strong indicator of changes in the average atomic number Z in tissues since hydrogen is the most abundant odd mass numbered nucleus present in living tissues. NMR is ideally suited for mapping relative hydrogen nuclear densities within living tissues.
In general, the principles of NMR are well known. All nuclei with an odd number of protons or neutrons behave, in effect, like small magnets. When placed in a steady external magnetic field, the magnetic axes of such nuclei (and hence of the atoms) precess at an angle about the imposed field axis at the so-called Larmor frequency. The Larmor frequency (f.sub.o) is related to the magnetic field (B.sub.0) at the nucleus by the equation f.sub.o =.gamma.B.sub.0 where .gamma. is a constant, the magnetogyric ratio characteristic of a particular type of nuclei.
Where a magnetic field gradient exists through an object, or if non-homogeneities exist in the imposed magnetic field, nuclei having the same magnetogyric ratio .gamma. will have different Larmor frequencies in accordance with their positions within the object. A volume of nuclei in the object can thus be conceptualized as having a range of precession frequencies centered about a given Larmor frequency.
It is convenient to view the nuclear process about to be described from a rotating frame of reference which rotates at the Larmor frequency such that a nuclear magnetic moment precessing at exactly the Larmor frequency appears to be substantially stationary. In this frame of reference, the macroscopic magnetization M is aligned with the direction of the imposed magnetic field B.sub.0. This is illustrated in FIG. 1A.
As is well known, the direction of net angular momentum or "spin" of a group of nuclei (and thus their net magnetic axis) can be reoriented with respect to the external magnetic field by electromagnetic signals having a frequency equal to the Larmor frequency. The electromagnetic signal produces a stationary magnetic field in the rotating frame of reference to nutate (reorient) the net spin of resonant (Larmor frequency) nuclei by an amount in accordance with its amplitude and duration. The direction of nutation is a function of the phase of the electromagnetic signal with respect to the nuclear precession about the imposed magnetic field. Thus, as illustrated in FIG. 1B, magnetic moment M has been nutated away from the Z axis.
Over a period of time, after removal of the electromagnetic signal, the many magnetic moments .mu. will realign parallel to external field B.sub.0. As nuclear realignment occurs, the relative phases of the individual spins (where phase is defined as the angle between the projection of the spin on a plane in the rotating frame of reference and an axis in this plane, which passes through the axis of rotation) begin to diverge as some nuclei precess faster and some slower than the central Larmor frequency. Thus, there is a gradual "dephasing" of the individual nuclear spins and a consequent loss of phase coherence. In a perfectly uniform magnetic field, such "dephasing", as illustrated in FIG. 1C, results from natural processes that cause nuclei to exchange energy with each other. The length of time that such "dephasing" takes to occur is related to the spin-spin, or transverse, relaxation time constant T.sub.2. In a non-uniform field, additional dephasing is caused by the different frequencies at different positions within the object. The time constant associated with the combination of this effect and T.sub.2 is known as T.sub.2 *.
During realignment, as illustrated in FIG. 1B, the nuclear moments .mu. also lose energy to their surroundings and thus relax, reorienting parallel to B.sub.0. This process is illustrated in FIG. 1D. The spin-lattice, or longitudinal, relaxation time constant T.sub.1, is related to this time of relaxation. Thus, as illustrated in FIG. 1E, after full relaxation, the macroscopic magnetization has reached its equilibrium value M.sub.0 and is aligned parallel to the imposed magnetic field B.sub.0.
Assuming the nuclear spins to be initially aligned as in FIG. 1A, and then reoriented transverse to the initial direction, as in FIG. 1B, the net nuclear magnetization in the X-Y plane (see FIG. 1B) will induce a characteristic RF signal in an appropriately oriented coil connected to an RF signal receiver. Initially upon reorientation, a relatively strong voltage is induced in the receiver coils which gradually decreases in amplitude due field inhomogeneity and to energy exchange between spins (the net relaxation time constant is T.sub.2 *). This signal is called the free induction decay (FID).
As is also well known, a "spin echo" or subsequent representation of the FID can be generated by bringing the respective spins back into phase coherence.
For example, if, at a time .tau. after the nuclear spins are reoriented (for example 90.degree. with respect to an initial direction) by a first electromagnetic pulse of appropriate frequency, magnitude and duration (hereinafter referred to as a 90.degree. pulse), another electromagnetic signal of appropriate frequency, magnitude and duration is applied to effect a 180.degree. nutation of the nuclear spins (hereinafter referred to as a 180.degree. pulse) each individual spin is effectively rotated by 180.degree. (in the rotating frame of reference). This means that the phase is now the negative of the phase accumulated before the 180.degree. pulse. The accumulation of further phase deviations for individual nuclear spins is the same as before and therefore, at time 2.tau. (after the initial disturbance) all of the individual spins again come into phase coherence (the negative phase cancels the further accumulated phase). In this manner, a so-called "spin echo" of the FID is generated. The peak amplitude of the spin echo is dependent upon the transverse relaxation time constant T.sub.2. The spin echo, in effect, comprises a mirror image and echo of the FID centered about a time 2.tau. after the initial disturbance.
It should be noted that the spin echo is always peak at a time period after the application of the 180.degree. pulse which is equal to the time interval between application of the initial disturbance (90.degree. pulse generating the FID) and the application of the 180.degree. pulse. This phenomenon shall hereinafter be referred to as the "rule of equal times."
Depending on the spin-spin relaxation time (related to T.sub.2), the FID following a selective 90.degree. RF pulse may continue for a relatively long period of time. In fact, at least part of the FID will continue through the spin echo following a selective 180.degree. RF pulse. Thus, the amplitude of the spin echo signal is in fact composed of two components: the spin echo from the unit volume, and part of the FID. Thus, since the amplitude of the spin echo signal is employed to determine the density of nuclei in the excited volume, the FID component will distort the spin echo signal, and therefore the measure of relative density related thereto.
For a more detailed description of the basic principles of NMR, reference is made to Farrar and Becker "Pulse and Fourier Transform NMR Introduction to Theory and Methods," Academic Press, New York, 1971.
While NMR techniques have long been utilized in the measurement of magnetic fields and in chemical analysis, NMR has only recently been applied to medical imaging applications. In general, NMR imaging techniques are based upon the premise that by purposefully disposing a specimen within a position-variant magnetic field (a field having an intensity which varies in accordance with position), the Larmor frequencies of the nuclei disposed at different positions are made to differ accordingly. Thus, a frequency discriminant is provided as between spins from atoms at differing positions, and the spin-density of a unit or element of volume within the excited volume of nuclei is represented by a particular frequency.
Imaging techniques utilizing NMR typically fall within five categories: imaging from projections; FONAR; sensitive point imaging; Fourier imaging; and imaging by selective irradiation.
The imaging from projections technique entails producing a multiplicity of projections from many different orientations by, for example, generating a linear field gradient within the object and recording a one dimensional projection of nuclear density in the direction defined by the gradient. An image is then reconstructed from the projections by mathematic techniques similar to those used in X-ray tomography. Such a method is described, for example, by Lauterbur, Nature, 242:190, March 1973.
The FONAR technique utilizes shaped magnetic fields applied across the object such that only a small resonant window within the sample produces an NMR signal. The sensitive region is then scanned through the object, for example, by physical movement. For a description of the FONAR technique, reference is made to Damadian et al., "Focusing Nuclear Magnetic Resonance (FONAR)" Visualization of a Tumor in a Live Animal, Science, Vol. 194, pp. 1430-1432, December 1976 and to U.S. Pat. No. 3,789,832 issued Feb. 5, 1974 to Damadian.
The sensitive point imaging technique, also known as spin mapping, is a method whereby the NMR signals from particular unit volumes are recorded in sequence. A magnetic field gradient, alternating at a predetermined low frequency (on the order of 50 Hz) is generated along one axis of the object. The NMR signals from all elements in the object are thus modulated at the frequency of the gradient change, with the exception of the protons located in the null plane (zero plane) of the gradient. Similar alternating gradients can be applied at asynchronous frequencies along transverse axes to, in effect, define a null point in the object at the intersection of the gradient null planes. Appropriate lowpass filtering thus provides an indication of the NMR signal from the point of intersection of the three null planes. Raster-type scanning of the object is provided by varying the relative gradients. Such a sensitive point imaging technique is described in Hinshaw, Journal of Applied Physics, Vol. 47, No. 8, August 1976.
A multiple sensitive point method utilizing two orthogonal alternating gradients to define a null line and a string of coherent, equally spaced phase alternated resonant radio frequency pulses, is alluded to in Andrew et al., "NMR Images by Multiple Sensitive Point Method, Application to Larger Biological Systems," Phys. Med. Biol. 1977, Vol. 22, No. 5, 971-974, 1977. It is stated that discrete Fourier transformation of the signal received between RF pulses is utilized to provide indicia of the proton density along the line of intersection of two alternating gradient null planes.
Fourier imaging techniques generally employ an initial RF pulse to reorient the spins of the protons in the object by 90.degree.. During the resultant FID signal, the object is subject to successive gradients applied consecutively in quick succession along the three principal Cartesian axes of the system. The FID signal is sampled in the presence of the last applied gradient, and a three dimensional Fourier transform is performed to develop a three dimensional image. Two dimensional Fourier transform methods are also known. For a discussion of the Fourier NMR techniques, reference is made to Kumar et al., "NMR Fourier Zeugmatography" Journal of Magnetic Resonance 18:69-83 (1975).
Imaging by selective irradiation techniques entails use of a sequence of electromagnetic pulses with predetermined frequency spectrums. A first magnetic gradient is applied along a given axis and the object is irradiated by a sequence of electromagnetic pulses having a combined frequency spectrum having equal intensity at all Larmor frequencies across the object with the exception of a narrow band. As a result of the irradiation, all of the nuclei within the object, with the exception of a narrow plane, will be saturated. The saturated atoms are thereby rendered non-responsive to further electromagnetic signals for a period of time on the order of the spin-lattice relaxation time constant T.sub.1. The first magnetic gradient is replaced by a gradient along an orthogonal direction and the object again irradiated by a sequence of electromagnetic pulses, this time having a bandwidth corresponding to a particular elementary strip within the unsaturated plane. The second sequence of pulses nutates the spins of the atoms within the predetermined strip by 90.degree., resulting in generation of an FID. The FID is then recorded in the presence of a magnetic gradient in the third orthogonal direction (along the direction of the strip) and a Fourier transform taken to provide the nuclear density distribution along the line. For a more detailed description of the imaging by selective irradiation, reference is made to U.S. Pat. No. 4,021,726 issued May 3, 1977 to Garroway et al.
For further descriptions of the above noted NMR imaging techniques, and other techniques, reference is made to the following articles:
P. C. Lauterbur et al., "Magnetic Resonance Zeugmatography" 18th Amper. Conf. 1974; P. Mansfield, P. K. Grannel & A. A. Maudsley, "Diffraction and Microscopy in Solids by NMR," 18th Amper. Conf. 1974, pp. 431-432; P. C. Lauterbur, "Magnetic Resonance Zeugmatography"; P. C. Lauterbur, "Flow Measurements by NMR Zeugmatography," Oct. 24, 1973; P. C. Lauterbur, "Stable Isotope Distributions by NMR," Proc. First International Conf. on Stable Isotopes Conf. 730525, May 9-18, 1973, pp. 255-260; P. C. Lauterbur, "Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance,"Nature, Vol. 242, Mar. 16, 1973, pp. 190-191; P. C. Lauterbur et al., "ESR Zeugmatography--Distributions of Unpaired Electrons Within Objects," Gordon Conf. Aug. 12-16, 1974; P. C. Lauterbur et al., "In Vivo Studies of Cancer by NMR Zeugmatography," Gordon Conf. Aug. 12-16, 1974; P. C. Lauterbur, "Reconstruction in Zeugmatography--The Spatial Resolution of Magnetic Resonance Signals," Intl. Workshop on 3-D Image Reconstruction Techniques, July 16-19, 1974; A. N. Garroway, "Velocity Profile Measurements by NRM," 18th Amper. Conf. 1974, pp. 435-436; W. S. Hinshaw, "The Application of Time Dependent Field Gradients to NMR Spin Mapping," 18th Amper. Conf. 1974, pp. 433-434; J. M. S. Hutchison, J. R. Mallard & C. C. Goll, "In Vivo Imaging of Body Structures Using Proton Resonance," 18th Amper. Conf. 1974, pp. 283-284; P. Mansfield & A. A. Maudsley, "Line Scan Proton Spin Imaging in Biological Structures by NMR," Phys. in Medicine and Biology 21 No. 5 (1976), pp. 847-852; P. K. Grannel, "NMR Body Images," Physics Bulletin, March 1976, pp. 95-96; P. C. Lauterbur, D. M. Krammer, W. V. House, C. Chen, "Zeugmatographic High Resolution NMR Spectroscopy, Images of Chemical Inhomogeneity Within Macroscopic Objects," American Chemical Society Journal, 97:23, Nov. 12, 1975; P. Mansfield & P. K. Grannel, "Diffraction and Microscopy in Solids and Liquids by NMR," Physical Review B, Vol. 12, No. 9, Nov. 1, 1975, pp. 3618-3634; P. Mansfield, A. A. Maudsley & T. Baines, "Fast Scan Proton Density Imaging by NMR," J. of Physics E, Vol. 9, 1976, pp. 271-278; P. C. Lauterbur, "Bibliography on Magnetic Resonance Zeugmatography," June 3, 1975; A. N. Garroway, P. K. Grannel & P. Mansfield, "Image Formation in NMR by a Selective Irradiative Process," J. Phys. C: Vol. 7, 1974, pp. 457-462; A. Kumar, D. Welt & R. Ernst, "NMR Fourier Zeugmatography," J. Mag. Res. 18, 69-83 (1975); P. Mansfield & A. A. Maudsley, "Medical Imaging by NMR," British Journal of Radiology 50, 188-194 (1977); D. I. Hoult, "Zeugmatography: A criticism of the Concept of a Selective Pulse in the Presence of a Field Gradient," J. Mag. Res. 26, 165-167 (1977); P. Mansfield & A. A. Maudsley, "Planar Spin Imaging by NMR," J. of Physics C., Vol. 9, 1976, pp. L409-412; P. Mansfield, "Proton Spin Imaging by Nuclear Magnetic Resonance," Contemporary Physics, Vol. 17, No. 6, 1976 pp. 553-576; R. Damadian et al., "Field Focusing Nuclear Magnetic Resonance (FONAR): Visualization of a Tumor in a Live Animal," Science, Vol. 194, 24 December 1976, pp. 1430-1431, E. R. Andrew, "Zeugmatography," IVth Amper. Summer School, September 1976; W. S. Hinshaw, "Image Formation by Nuclear Magnetic Resonance: The Sensitive-Point Method," J. of Applied Physics, Vol. 47, No. 8, August 1976; R. Damadian, M. Goldsmith & L. Minkoff, "NMR, in Cancer: XVI FONAR Image of the Live Human Body," Physiol. Chem. and Phys. 9, (1977), pp. 97-108; G. N. Holland & P. A. Bottomley, "A Colour Display Technique for NMR Imaging," J. of Physics E: 10 (1977), pp. 714-716; T. Baines & P. Mansfield, "An Improved Picture Display for NMR Imaging," Journal of Physics E: Scientific Instruments 9 (1976), pp. 809-811; E. R. Andrew et al., "NMR Images by the Multiple Sensitive Point Method: Application to Larger Biological Systems," Physics in Medicine and Biology 22, No. 5, 917-974 (1977); L. Minkoff, R. Damadian, T. E. Thomas, N. Hu, M. Goldsmith, J. Koutcher & M. Stanford, "NMR in Cancer: XVII. Dewar for a 53-Inch Superconducting NMR Magnet," Physiol. Chem. and Phys. 9 (1977), pp. 101-109, Ros Herman, "NMR Makes Waves in Medical Equipment Companies," New Scientist, Jan. 12, 1978; L. E. Crooks, T. P. Grover, L. Kaufman & J. R. Singer, "Tomographic Imaging with Nuclear Magnetic Resonance," Investigative Radiology, 13, 63 January -February 1978; W. S. Hinshaw, P. A. Bottomley & G. N. Holland, "Radiographic Thin-Section Image of the Human Wrist by Nuclear Magnetic Resonance,"Nature, Vol. 270, No. 22, 29 December, 1977, pp. 722-723; and T. C. Farrar & E.D. Becker, "Pulse and Fourier Transform NMR--Introduction to Theory and Methods," Academic Press, 1971, New York, pp. 1-33.
Further reference is made to U.S. Pat. Nos. 3,975,675 issued to Dunand et al. on Aug. 17, 1976; 4,021,726 issued to Garroway et al. on May 3, 1977; 4,015,196 issued to Moore et al. on Mar. 29, 1977; 4,034,191 issued to Tomlinson et al. on July 5, 1977; 3,789,832 issued to Damadian on Feb. 5, 1974; 3,932,805 issued to Abe et al. on Jan. 13, 1976; 3,651,396 issued to Hewitt et al. on Mar. 21, 1973; and 3,999,118 issued to Hoult on Dec. 21, 1976.
It should be appreciated that each of the above described techniques is disadvantageous in various aspects. For example, techniques developing an image from projections require extensive mathematical processing of the data. The FONAR technique apparently requires either an extremely complex system to scan the magnetic field, or some means for generating relative movement between the field and the subject.
The three dimensional Fourier transform techniques require that all planes be scanned simultaneously a multiplicity of times in order to develop sufficient data so that data from the various planes can be mathematically separated. In two dimensional Fourier transform techniques the repetition rate is limited by the T.sub.1 spin-lattice relaxation time of the nuclei since each irradiation affects the entire spin system. Further, large amounts of computer storage are required.
Imaging techniques utilizing selective irradiation wherein the entire object is saturated with the exception of a single plane are disadvantageous in that such systems cannot readily be adapted for rapid sequential scanning of multiple planes. That is, before a second plane can be addressed a sufficient time must pass for the object to become unsaturated.
The present invention is directed to a technique utilizing selective irradiation of the object by electromagnetic pulses to generate spin echoes (as opposed to the detection of the free induction decay signals (FID)) to readily provide for rapid multiple plane scanning.
In general, as noted above, the phenomenon of spin echoes is well known. In the past, however, the spin echo has been used primarily for measurement of the transverse relaxation time constant T.sub.2 of a specimen. An example of a system utilizing spin echoes for the measurement of the relaxation time T.sub.2 in logging earth formations traversed by a bore hole, is described in U.S. Pat. No. 3,128,425 issued Apr. 7, 1964 to Codrington. Similarly, U.S. Pat. No. 3,213,355 issued to Woessner on Oct. 19, 1965 describes a system for measuring the dimensions of a container utilizing spin echoes to determine the transverse relaxation time T.sub.2.
Mansfield and Maudsley, "Planar Spin Imaging by NMR," J. Phys. C: Solid State Physics, Vol. 9, 1976 (noted above), appears to indicate that after an FID has decayed, various signal-refocusing arrangements (selective 180.degree. pulses, 90.degree. pulses and various combinations with field gradient reversals) may be employed to recall the signal for signal averaging purposes. The specific mechanism of the refocusing arrangements, however, is not described in the article. In a similar vein, U.S. Pat. No. 3,781,650 issued Dec. 25, 1973 to Keller appears to describe an NMR spectrometer wherein FIDs and spin echoes are combined for purposes of interference reduction.
Also, in the aforementioned communication by Hoult (Journal of Magnetic Resonance, 26: 165-167 (1977)), it is stated that the selective irradiation techniques violate the "Uncertainty Principle" unless non-linearities present in the NMR system are exploited. Hoult states that a square selective pulse contains a wide spectrum of frequencies, and that during the time the pulse is applied the "flipped spins" dephase. However, he further contends that the situation is not irretrievable in that if the field gradient is reversed after the pulse, an echo of the pulse is formed, and in the middle of the echo for small phase angle pulses, all of the spins are in phase.
Hoult's communication implies that the shape of the selected region is essentially identical to the shape of the spectrum of the selective irradiation. However, the present inventors have noted that since the response of nuclear spins to RF magnetic field is non-linear that the shape of selected volume does not exactly correspond to the shape of the spectrum of the exciting RF magnetic field. For example a spectrum with a perfectly square block of frequencies will excite a volume which covers a frequency range slightly wider than the block of frequencies and the edges of the excited volume are sloped rather than vertical. The shape of the excited volume can be calculated using the Block equations, described in Farrar and Becker pages 7 and 8, with an appropriate time dependent RF magnetic field having the frequency spectrum being considered. The use of the Block equations also determines the spin dephasing which occurs during the RF pulse. It can be shown, thus, that Hoult's gradient reversal suggestion works even for flip angles that are not small. For a 90.degree. flip angle the gradient reversal needed to achieve a maximum signal from the spins in the selected volume is a reversed gradient with the same strength as the original but with a duration which is about half the duration of the irradiation. The exact duration of the reversal gradient is dependent on the shape of the RF pulse. The effect of this reversed gradient is to recluster most of the spins which dephased during the selective irradiation. Since the dephasing during the selective irradiation is not linear the rephasing is not perfect, but it is substantial. After the termination of the reversed gradient one has a signal which we will consider to be an FID although Hoult calls it an echo. The other large flip angle which will be frequently used is 180.degree.. A selective irradiation of this value requires no phase correction. The reason is that spin dephasing during the first 90.degree. of the flip is cancelled by rephasing during the second 90.degree. of the flip.
The gradient reversal after a selective irradiation is one of several types of phase corrections necessary to the operation of the line mapping techniques described herein. Application of a reversed gradient for a period about half the duration of the selective irradiation will be hereinafter referred to as Type I phase correction. In practice the area under the correction gradient versus time waveform is the critical factor. If the correction gradient were twice as strong it would only have to be applied for half the time. This applies to all the types of phase corrections and the descriptions use the example of equal strength only for simplicity. A second type of phase correction, hereinafter referred to as a Type II phase correction, is immediate correction for a gradient pulse that has just ended; the phase spreading which occurs in parts of the object not subject to a selective irradiation during the application of this gradient pulse is corrected by the immediate application of an equal and opposite gradient for the same amount of time as the original gradient pulse. An extension of a Type II phase correction is to allow a delay time before the correction gradient is applied. Events such as spin echoes may be observed during this delay time. Such a phase correction wherein an opposite polarity gradient is applied after a delay time will be referred to as a Type III phase correction. A further type of phase correction (Type IV) is similar to a type III correction, except that a 180.degree. RF pulse is applied to the volume of interest during the period between the application of the original and correction gradients, such that the polarity of the correction gradient will be the same as that of the first gradient. The correction gradient has the same polarity as the first gradient because the intervening 180.degree. RF pulse makes the phases negative.